The purpose of this project is to define the mechanisms by which the epithelium of pulmonary conducting airways of primates differentiates and matures. Emphasis will be on the role of cellular interactions, epithelial-to-epithelial and mesenchymal-to-epithelial, which determine the differentiation from a single cell type in the fetus to eight in the adult. The pattern of epithelial differentiation will be delineated, shifts in population densities measured, changes in organelles and inclusions characterized, and intermediate forms identified. The pattern of development of the underlying mesenchyme will be defined and correlated withepithelial changes. Once critical points in differentiation are identified, epithelial-epithelial and mesenchymal-epithelial junctional contancts will be studied. The rhesus macaque (Macaca mulatta) will be used because of the close similarities of its tracheal, bronchial, and bronchiolar epithelium to that of man. Lungs from all three phases of fetal lung development, pseudoglandular, canalicular, and terminal sac, will be studied by high resolution light microscopy, and transmission and scanning electron microscopy. Specific airway generations will be identified by microdissection. The same exact airways will be examined from each fetal lung. This project will attempt to thoroughly evaluate the epithelial maturation of conducting airways at the cellular level in primate lung and to correlate it with simultaneous events in the surrounding mesenchyme. These events will be followed in the same airway branches throughout fetal development and simultaneously in different generations (trachea, extra- and intrapulmonary bronchi, and terminal and respiratory bronchioles) of conducting airway in the same lung.